Diabetes mellitus is associated with degenerative changes of small blood vessels. The etiology of these micro-vascular changes remain uncertain and is controversial. Studies of the accelerated vascular changes in young diabetic subjects may lead to a better understanding of the vasular diseases commonly observed in the general population. The study proposed is designed to continue long term longitudinal studies of children with chemical and overt diabetes to determine the interrelationship between early recognition and metabolic control of the diabetes and the time of appearance and rate of progression of the micro-vascular changes known to occur with the disease. Vascular status is being determined in both normal and diabetic children of comparable ages by measuring with the electron microscope the thickness of the capillary basement membranes (CBMT) from muscle biopsies. Retinal studies also are being performed on selected subjects to correlate the degree of CBMT with early vascular changes in the eye grounds. These retinal changes often begin to appear 15 to 20 years after the onset of clinical (overt) diabetes. In this proposal, diabetic subjects from two clinics (Columbia, Mo. and Pittsburgh, Pa.) will be studied to provide two comparable groups of subjects except for the degree of control of their diabetes. Additional data are necessary from both normal and diabetic subjects in order to provide a sufficient number of observations to verify statistically if there is a definite relationship between the degree of control of the disease and rate of progression of the micro-vascular changes. Data to date indicate that the rate of CBMT is related primarily to the degree of control of the diabetes and that changes occur more rapidly in girls than in boys of comparable age.